3D analysis of apical dendritic organization in the prefrontal cortex of young and old monkey

Its known that the age-related decline in cognitive facilities is not due to the loss of neurons but more subtle changes in specific areas of the brain. Structural and morphological changes in cellular alignment in the minicolumns correlate with increased prevalence of neurological diseases and in aging. In the rhesus monkey, cognitive decline is similar to what humans experience in aging. In the monkey prefrontal cortex, Brodmann area 46, an important region for executive functioning, cognitive decline correlates with changes in cellular alignment or “columnar strength” as studies by Cruz et al., (2009). Using the density maps method in Area 46, the ventral bank was identified to be the most susceptible to structural changes. Minicolumns, are defined by the cellular alignment of neurons in the cortex and some believe that the dendritic bundles of neurons in the cortex is also considered an integral part of the columns. The functional role of apical dendrites, is not well understood, however, given the that repeated organized bundles transverse through the laminae could be further support for their inclusion in minicolumns with possible functional importance. If structural changes such as loss of columnar strength (neuronal displacement) that correlates with cognitive aging, it is possible that the dendritic organization may also be affected in this area. In this thesis, it is hypothesized that the dendritic bundles in this area could also be related to the cognitive deficits associated with normal aging. Using double- fluorescence labeling for dendrites (MAP-2) and neurons (Neu-N), 3D confocal reconstructions of the dorsal and ventral banks of Area 46 were used to investigate structural/morphological changes in the dendritic bundles in young and old rhesus monkeys. While cortical thickness and apical dendritic length between both banks did not change, we found a significant increase in inter-bundle spacing at layer 6A in the older monkeys in the ventral bank. Inter-bundle spacing for bundles in layer 5 was measured and showed that the young consistently have smaller inter-bundle spacing. Future studies with larger sample size will also investigate whether changes in dendritic bundles and their organization also correlate with age-related cognitive deficits

FSH blockade improves cognition in mice with Alzheimer\u27s disease

Alzheimer\u27s disease has a higher incidence in older women, with a spike in cognitive decline that tracks with visceral adiposity, dysregulated energy homeostasis and bone loss during the menopausal transition. Inhibiting the action of follicle-stimulating hormone (FSH) reduces body fat, enhances thermogenesis, increases bone mass and lowers serum cholesterol in mice. Here we show that FSH acts directly on hippocampal and cortical neurons to accelerate amyloid-β and Tau deposition and impair cognition in mice displaying features of Alzheimer\u27s disease. Blocking FSH action in these mice abrogates the Alzheimer\u27s disease-like phenotype by inhibiting the neuronal C/EBPβ-δ-secretase pathway. These data not only suggest a causal role for rising serum FSH levels in the exaggerated Alzheimer\u27s disease pathophysiology during menopause, but also reveal an opportunity for treating Alzheimer\u27s disease, obesity, osteoporosis and dyslipidaemia with a single FSH-blocking agent